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T. Elber. California Institute of Technology.

In several studies purchase levitra extra dosage with a visa erectile dysfunction medications comparison, prior hysterectomy and prior reconstructive surgery were more common in those with pessary fitting failure [10 discount 60mg levitra extra dosage fast delivery erectile dysfunction causes medications,18 cheapest levitra extra dosage erectile dysfunction protocol scam or real,19] purchase 40mg levitra extra dosage with mastercard erectile dysfunction shots. Possible anatomic predictors include a wide introitus (>4 fingerbreadths), short vaginal length (<7 cm), and larger genital-hiatus-to-vaginal-length ratio [14,20]. Among postmenopausal women, use of vaginal estrogen therapy may increase fitting success rates [19]. Many pessary providers report tailoring their choice of pessary to specific support defects [3], but this practice is based on limited evidence. Many published protocols use the ring or ring with support pessary as a first choice pessary in all patients because of its ease of use and reserve other pessary types (most often Gellhorn, donut, or cube pessaries) for women unable to retain or to be comfortably fitted with a ring [10,14,22,23]. Iowa Pessary Protocol Given the few published studies on pessary treatment, the literature cannot guide clinicians in choosing pessary management strategies. Therefore, much of clinical pessary practice is based on clinical experience and expert opinion. Here, we present the pessary protocol used at the University of Iowa Urogynecology Clinic. Prior to fitting a pessary, we treat most women that demonstrate vaginal atrophy for 6 weeks with vaginal estrogen therapy, as this may increase the likelihood of a successful pessary fitting [19]. Similar to other reported protocols [10,14,22], we begin by trying to fit a ring or ring with support pessary as these are easy for providers to fit and for patients to self-manage. If unable to fit either a ring or Gellhorn pessary, other types (commonly a donut or cube) are tried. An appropriately fitting pessary should fill the vagina, but allow the clinician’s finger to easily sweep between the pessary and the vaginal wall. After finding a pessary with a good fit, we instruct women to do vigorous activity in the clinic area (such as brisk walking and straining) to ensure that the pessary is retained in the vagina and is comfortable. We also ask that women attempt to void with the pessary in place before leaving the office. In postmenopausal patients without contraindications to hormonal therapy, low-dose vaginal estrogen is often prescribed. In most cases, patients are scheduled for an initial follow-up appointment within 2 weeks. Women fitted with a cube pessary are asked to return sooner (within 1 week) because of an increased risk of vaginal erosions [22], which in our experience may occur rapidly. At each subsequent pessary appointment, patients are first examined with the pessary in place to ensure correct fit and placement in the vagina. We recommend turning the speculum 90° to visualize the anterior and posterior surfaces carefully. After an initial 2-week and 3-month check, we examine women who manage their own pessary yearly. In contrast to reports from some centers [14,22], we find the majority of women can be instructed to remove and replace their pessaries at home. We recommend women remove the pessary once or twice weekly, leave it out overnight, and then reinsert it in the morning. Women rarely encounter excessive or malodorous vaginal discharge using this approach. If women are unable or unwilling to remove the pessary at home, they are seen at regular intervals in the office for pessary removal and examination. In these patients, we gradually increase the office visit interval after the initial follow-up visit to a maximum interval of 3 months. Women who develop increasing vaginal discharge or erosions over shorter intervals will need more frequent follow- up. Visiting nurses can be an invaluable resource for women unable to care for the pessary on their own. They are often able to visit the woman at home, remove the pessary in the evening, and return in the morning to replace it. Excessive or foul-smelling discharge, increased discomfort, or vaginal bleeding signals a need to arrange medical follow-up. Pessaries used to treat incontinence frequently have 679 a knob that is placed under the urethra (Figure 44. Some of the most commonly used incontinence pessaries include the incontinence dish (with or without support) and the incontinence ring with knob (with or without support) (inset, Figure 44. Flow rates did not decrease, and voided and postvoid volumes were unchanged with the pessary, suggesting that urethral obstruction did not occur. At urodynamics, maximal urethral closure pressures did not increase (as seen in previous studies), but functional urethral length did increase. Contrary to prior findings [24], 680 maximal flow rates decreased and detrusor pressures increased, suggesting increased urethral resistance, although postvoid volumes were not elevated. Increasing urethral resistance and elevation of the bladder neck may also help restore continence. Effectiveness Few controlled trials have been published evaluating the use of incontinence pessaries. Both devices significantly decreased urine loss (measured with a pad test) during exercise when compared to the control session. Better outcomes were seen with both devices in women who had milder urine loss [27]. In total, 450 participants with stress- predominant urinary incontinence were randomized to incontinence pessary, behavioral therapy with pelvic muscle training, or a combined treatment arm. In two retrospective studies (including 100 and 190 patients), about 60% chose to undergo a pessary fitting for stress or mixed urinary incontinence, and 85%–90% were successfully fit [29,30]. Of those successfully fit with a pessary, 55%–60% continued using the pessary (median duration of follow-up 11–13 months). In contrast to these findings, in a small prospective study, only 16% of 38 women fit with an incontinence ring with support pessary chose to continue use out to 1 year [31]. In the few that continued the use, the pessary resulted in fewer leaking episodes and 9 (24%) were subjectively “dry. Placement of a menstrual tampon has similar moderate levels of success (57% continent during use) in treating exercise-induced incontinence [27]. In a small study (32 women), a novel bell-shaped self-positioning incontinence pessary (Uresta, EastMed, Inc. One reusable device available in Australia and Europe (Contiform International, Blacktown, New South Wales, Australia) is shaped like a large hollow tampon [35]. The device, designed to be fitted and self-managed by patients, can be reused for 30–60 days. In a small study of this device, 54% of women who completed the treatment period were dry. The Contrelle Activgard (Codan, Kobenhavn, Denmark) is a polyurethane foam tampon. In the 50 women who completed the 4-week trial, 92% were subjectively continent [37]. Urethral inserts and external urethral occlusive devices function as mechanical barriers to prevent urinary leakage. These devices require highly motivated and manually dexterous patients as the devices must be removed to urinate and then replaced after each void. Studies suggest they have lower overall success rates than seen for some of the vaginal devices, partly because of higher dropout rates [38]. Urethral inserts are sterile, single-use devices placed into the urethra by the patient and held in place by an inflated balloon at the bladder neck. Such inserts are appropriate for women with no history of recurrent urinary tract infections and no serious contraindications to bacteriuria (e. Multicenter studies demonstrate high rates of continence with urethral inserts in place (80%–95%) and high rates of satisfaction in women who continue use, but overall results are limited by high withdrawal rates and frequent adverse events [39,40]. External urethral occlusive devices fit over the external urethral meatus and are held in place by adhesive or suction. These devices have fewer reported side effects than the urethral inserts, but reported continence rates are lower (40%–50%) [41,42]. Patient acceptability of this type of device, similar to urethral inserts, appears to be limited. Several types have been marketed in the United States in the past, but none are currently commercially available. In a 5-year prospective study, 12% of pessary users experienced minor complications (including pain or discomfort, vaginal excoriation or bleeding, and constipation) [15]. Vaginal discharge, odor, and vaginal infections may also occur in pessary users, but these are infrequent reasons for discontinuing the use [22,29]. Erosions may be more common in women with hypoestrogenic vaginal changes and in those using a cube pessary. In one case series, erosions developed in 5 of 6 women using cube pessaries, but in only 3 of 101 women using ring pessaries [22]. Vaginal erosions due to pessary use typically can be managed by removing the pessary more frequently, suspending use entirely for some period of time (e. If erosions recur, a change to a different size or type of pessary may be necessary. Symptomatic vaginal discharge associated with pessary use may be treated with antibiotics and vaginal estrogen treatment or by suspending pessary use until symptoms resolve. Some clinicians routinely recommend the regular use of vaginal products for vaginal acidification or lubrication to decrease vaginal discharge or odor symptoms in pessary users, but minimal evidence exists to support or refute this practice.

They can help determine the limits and vascular involvement of solid masses order levitra extra dosage online now erectile dysfunction treatment in vadodara, which is critical when a tumor is posterior and dangerously close to the inferior vena cava or the origins of hepatic veins cheap levitra extra dosage 40 mg on line effexor xr impotence. Fibrin glue (Tisseal purchase discount levitra extra dosage on line erectile dysfunction aids, Baxter Inc purchase levitra extra dosage 60 mg on line impotence ginseng, Deerfeld Il) is used and can be very effcient in achieving complete hemostasis after laparoscopic hepatic resection. It should be applied without pressure to the raw surfaces of the liver at the end of the resection. The surgeon stands Positioning the between the patient’s lower limbs, which are spread and placed in sequential compres- Patient and sion devices on padded supports to avoid deep venous thrombosis and pressure necro- Operating Team sis. This arrangement is comfortable for the surgeon, who does not have to bend unnecessarily, which may occur when he or she is standing to the side, and it provides a symmetric view of the monitors. The monitors are placed on each side of the anesthesiologist near the head of the patient. The scrub technician stands to the right of the surgeon, beside the camera assis- tant, allowing him or her to pass instruments to the surgeon’s right hand. All traditional instruments for open surgery must be at hand in case immediate conversion becomes necessary. Access to the A minimum of four ports must be introduced for basic liver procerdures (beyond simple Liver diagnostic laproscopy). The ports are placed to allow enough space between them to avoid the knitting needle effect between the various instruments. The port for the lapa- roscope is usually introduced at the umbilicus, the port for the graspers on the right side, and the port for the operating instruments on the left side of the patient. This triangle is enlarged to a rectangle by placing a fourth port for palpation and/or the irrigation/aspi- ration probe (Fig. This arrangement can be varied according to the location of the lesion and the working method to which the surgeon is accustomed; there is no “ideal” arrangement of the ports for this type of surgery. All ports must be at least 10 mm to allow the camera to be moved from port to port to visualize the hepatic lesion from different angles. Further trocars can be introduced for specifc instruments – fve or six is realistically the maximum number of trocars if the operating feld is not to be overcrowded. This allows two surgeons to perform simul- taneously with a “four-handed” approach (Fig. This four handed approach minimizes hemorrhage and speeds up the proce- dure (Fig. A umbilical scope; B surgeon’s left hand; C surgeon’s right hand; D suction irrigation device or for retraction. Maneuvers This is the key to successful surgery as it clears the area surrounding the lesion allowing Common to All direct access. Laparoscopic The frst step is division and ligation of the round and falciform ligaments between Liver Surgery clips, with a vascular stapler, or with the harmonic shears so that the anterosuperior surface of the liver can be pushed down. Retraction of the liver is achieved with a fan retractor held by an assistant, while the surgeon brings the harmonic shears above the liver and divides the triangular ligament under direct view. The left triangular ligament is divided if the lesion is on the left lobe, or partial division of the right triangular liga- ment (which is more diffcult) for a right posterior lesion. During a major resection, such as a left lateral segmentectomy, it is necessary to be able to approach the side of the supe- rior vena cava to control the hepatic veins, in particular the left hepatic vein. Once the liver is completely mobilized an incision is made in Glisson’s capsule, using the harmonic shears (Fig. An ultrasonic dissec- tor is very handy here, enabling parenchymal destruction while preserving the vascular and ductal elements. All large vascular vessels must be controlled by clips or by ties in the case of a major vessel or biliary duct. At the end of the operation, the liver segment must be placed in a suitable retrieval bag that allows extraction without spillage of liver cells. Other extraction sites are possible; for larger specimens, a suprapubic incision can be used, or in the case of hand-assisted techniques, the extraction site is the same as the incision used for the introduction of the gelport and the nondominant hand (depicted here on the right side of the patient, Fig. A faliciform ligament; B left triangular ligament; C right trian- gular ligament 54 Chapter 4  Laparoscopic Liver Surgery Fig. The liver specimen should never be reduced to a total mush, which would not allow postoperative pathological examination. Diagnostic laparoscopy can be used to look for small tumors of the liver that may not Diagnostic be detectable by conventional imaging techniques. Pancreatic cancer, for example, is Laparoscopy often accompanied by small multiple hepatic metastases that are spread throughout the entire organ. Because of their small size, these and other intraperitoneal seedings are sometimes undetectable by standard imaging methods, but can usually be seen with a laparoscope. This can change the indication from a curative resection to palliative sur- gery, or even to nonintervention in very advanced cases. Diagnostic laparoscopy is also useful in identifying liver involvement unseen by preoperative imaging in cancer of the gallbladder. The diagnostic procedure involves a laparoscope introduced via an umbilical port, with another port to allow for biopsy. Users who have suffcient experience can produce images that are as helpful as images obtained by intraoperative open ultrasonography. Laparoscopic ultrasonography enables the detection of deeper lying metastases as well as underlying connections to vital struc- tures such as the hepatic veins. With intraoperative ultrasonography, a biopsy can be directed without fear of causing major hemorrhaging or bile leaks. This is a relatively easy procedure; for single giant cysts, the basic trocar approach is used Fenestration of (Fig. The harmonic shears are used to fenestrate the cyst after incising its most Liver Cysts protuberant area. Clips should be placed to ensure hemostasis, as the number one postoperative problem is bleeding from the liver edge. If the cyst is very large with a thick membrane, a linear cutter with vascular loads can be used to achieve this resection at the liver edge. In the case of polycystic liver dis- ease, the operation proceeds with the same technique through previously unroofed cysts; however, when dealing with deeper cysts, care should be exercised to avoid injury to a hepatic vein or pedicle, as these vascular structures have a similar appearance as that of liver cysts under the illumination of the laparoscope (transparent with a bluish tinge). Enucleation, wedge resection, anterior segmentectomies, and left lateral segmentecto- Resection of mies are reasonable laparoscopic technical possibilities. Lobectomies are very advanced Liver Tumors procedures reserved for a few laparoscopic liver experts (Fig. A enucleation; B atypical peripheral wedge; C segmentectomy; E left lateral sectoriectomy; D lobectomy Limited Resection of Minor Lesions Wedge resection of a solid benign tumor, such as an adenoma, is a good example of a small lesion that can be removed laparoscopically. A small metastasis in the left lobe also can be safely resected under laparoscopy with a reasonable 15–20 mm surgical margin. Four trocars are necessary for access: an umbilical trocar for the laparoscope, two large trocars for the grasping forceps and other instruments, and one sub-xiphoid trocar for the irrigation/aspiration probe. For a larger resection it is necessary to use the “four- handed approach” described above (Fig. Smoke must be sucked out intermittently through the irrigation/aspiration cannula. It is then nec- essary to dissect progressively deeper into the hepatic parenchyma using the harmonic shears while separating the edges of the liver with the left handed forceps. Sometimes a ffth trocar is needed for the assistant to insert a grasper to carefully move the tumor mass. Atraumatic grasping forceps allow the minute structures to be coagulated as they pass through this groove. All bile ducts should be clipped or tied; it is not recommended to rely on the harmonic shears to seal bile ducts, as this can lead to postoperative bile leaks. Clips must be employed for larger vessels, and it is recommended that a double clipping technique be used to avoid inadvertent dislocation of a single clip on a vascular pedicle. The irrigation/ aspiration probe should be used in a deep groove in the liver to keep the operating feld dry. The need to maintain a bloodless feld by means of constant rinsing of the dissection area cannot be overemphasized. A 5–8 cm solid tumor can be extracted in a bag without diffculty by enlarging the fascial incision at the umbilicus so that the extracted specimen is left intact. Left Lateral Segmentectomy This approach is aimed at larger tumors on the left lobe for which a wedge resection or limited segmentectomy may prove to be incomplete and therefore inadequate treatment. Larger lesions of the left lobe may also be best dealt with by a formal resection when a wedge procedure might actually prove to be more diffcult and hazardous. Laparoscopic left lateral segmentectomy, however, should only be considered by surgeons who have extensive experience in both laparoscopy and liver surgery. This allows for simultaneous maneuvers by two surgeons operating in harmony (four hands approach) - one doing the dissection and the other concentrating on hemostatic control and the clipping of all ves- sels. The lead surgeon usually operates the ultrasonic dissector while the second surgeon applies clips and divides the isolated vessels. This includes the left hepatic vein which must be iso- lated before the liver capsule is incised. A Pringle maneuver can then he performed using an atraumatic right-angled dis- sector, and a tourniquet is placed around the porta hepatis (Fig. Then, after full mobilization of the left triangular ligament, it is possible to retract the left lobe inferiorly using an atraumatic fan retractor allowing one to see the insertion of the left hepatic vein on the vena cava. This is an extremely dangerous maneuver and should be done only by a very skilled laparoscopic surgeon. Now a right-angled atraumatic dissector is introduced and the left hepatic vein is encircled using gentle blunt dissection and a long tie placed around it. An atraumatic clamp should always be kept handy in the vicinity in case there is bleeding that requires immediate compression and clamping. Therefore, unless this vessel is safely controlled within seconds of hemorrhaging, the surgeon should opt for an immediate safe conversion.

This can be life threatening with preexisting hyperkalemia or in patients who have suffered burn injury cheap 40mg levitra extra dosage erectile dysfunction drugs associated with increased melanoma risk, massive trauma buy levitra extra dosage 60 mg cheap erectile dysfunction by age statistics, or other conditions buy levitra extra dosage 60mg free shipping erectile dysfunction drugs mechanism of action. Muscle pains are sometimes noted postoperatively after succinylcholine administration purchase levitra extra dosage cheap erectile dysfunction shakes menu. Elevation of intracranial, intragastric, and intraocular pressures have been reported. Prolonged action (discussed on front side of card) Malignant hyperthermia can be triggered in susceptible patients by succinylcholine. Maintaining neuromuscular blockade can be done by administering intermittent boluses or by continuous infusion but should be guided by a nerve stimulator and clinical signs. Potentiation can occur by volatile anesthetics (10%–15% dose reduction) and by adding other nondepolariz- ing neuromuscular blockers (more than additive). Additionally, hypothermia, respiratory acidosis, hypoka- lemia, hypocalcemia, and hypermagnesemia can prolong a nondepolarizing block. In general, the diaphragm, jaw, larynx, and facial muscles (orbicularis oculi) respond to and recover from muscle relaxation sooner than the thumb. Side effects include histamine release and autonomic effects, depending on the drug. Renal excretion is significant in clearing doxacurium, pancuronium, vecuronium, and pipecuronium. Side effects: Histamine release (hypotension, tachycardia, bronchospasm), laudanosine toxicity (breakdown product of Hofmann elimination that can cause central nervous system excitation and is metabolized by liver), prolonged action (at abnormal pH and temperature). Cisatracurium (benzylisoquinoline; stereoisomer of atracurium) Metabolism and excretion: Same as atracurium. Side effects: Laudanosine toxicity (significantly lower levels than with atracurium), prolonged action (at abnormal pH and temperature). Vecuronium (steroidal) Metabolism and excretion: Excretion is primarily biliary and secondarily renal (25%); limited liver metabolism. Gantacurium (chlorofumarate) Metabolism and excretion: Cysteine adduction and ester hydrolysis. Nondepolarizing muscle relaxants: Neuromuscular transmission is blocked by nondepolarizing muscle relaxants that bind to postsynaptic nicotinic cholinergic receptors. Reversal of Nondepolarizing Muscle Relaxants Spontaneous reversal: Occurs with gradual diffusion, redistribution, metabolism, and excretion of nonde- polarizing muscle relaxants. Pharmacologic reversal: Occurs with the administration of specific reversal agents. Reversal with acetyl- cholinesterase inhibitors should be monitored with a peripheral nerve stimulator. Cardiovascular system: The predominant muscarinic effect on the heart is a vagal-like bradycardia that can progress to sinus arrest. Pulmonary receptors: Muscarinic stimulation can result in bronchospasm and increased respiratory secre- tions. Gastrointestinal receptors: Muscarinic stimulation increases peristaltic activity (esophageal, gastric, and intestinal) and glandular secretions (e. Perioperative bowel anastomotic leakage, nau- sea and vomiting, and fecal incontinence have been attributed to the use of cholinesterase inhibitors. Onset: Effects apparent in 5 to 10 minutes; peak at 10 minutes and last more than 1 hour. If used with glycopyrrolate, should be given several minutes after glycopyrrolate so that onset time matches. Clinical note: Can be used to treat central anticholinergic toxicity from scopolamine or atropine overdose. Clinical note: Because of concerns about hypersensitivity and allergic reactions, not yet approved by the U. Clinical pharmacology: Extent of anticholinergic effect depends on the degree of baseline vagal tone. Presynaptic muscarinic receptors on adrenergic nerve terminals are known to inhibit norepinephrine release, so antagonism may modestly enhance sympathetic activity. Inhibit the secretions of the respiratory tract mucosa Relaxation of the bronchial smooth muscle Reduces airway resistance Increases anatomic dead space Cerebral: Spectrum of effects depending on drug and dosage. Absorption by vessels in the conjunctival sac is similar to subcutaneous injection. Systemic manifestations include dry mouth, tachycardia, atropine flush, atropine fever, and impaired vision (although not in this case). What other drugs possess anticholinergic activity that could predispose to the central anticholinergic syn- drome? Tricyclic antidepressants, antihistamines, and antipsychotics have antimuscarinic properties that may potentiate the side effects of anticholinergic drugs. Cholinesterase inhibitors indirectly increase the amount of acetylcholine available to compete with anticho- linergic drugs at the muscarinic receptor. In contrast, physostigmine, a tertiary amine, is lipid soluble and effectively reverses central anticholinergic toxicity (an initial dose of 0. If the anticholinergic overdose were accompanied by tachycardia, fever, and so on, it would be prudent to postpone the surgery in this elderly patient. However, if the patient’s mental status responds to physostigmine and there are no other apparent anticholinergic side effects, it would be reasonable to proceed. These receptors are widely distributed throughout the body, and their effect depends on end-organ distribution. Alpha-2 adrenergic receptors: Principle function is as presynaptic autoreceptors, which decrease adenylate cyclase activity, thus decreasing calcium entry into neuronal terminal, limiting subsequent exocytosis of storage vesicles containing norepinephrine. This negative feedback mechanism reduces endogenous norepinephrine release from central nervous system neurons, causing sedation, decreased sympathetic outflow, and subsequent peripheral vasodi- lation with decreased systemic vascular resistance. They function to increase adenyl- ate cyclase activity, converting adenosine triphosphate to cyclic adenosine monophosphate, thus initiating a kinase phosphorylation cascade. Beta-1 agonists cause increased chronotropy, dromotropy (increased conduction velocity), and inotropy. Beta-2 adrenergic receptors: Mostly postsynaptic receptors located in smooth muscle and gland cells. Beta-2 agonists also cause glycogenolysis, lipolysis, gluconeogenesis, and insulin release. Beta-2 receptors activate the Na-K pump, driving potassium intracellularly, which can lead to hypokalemia and arrhythmias. Clinical Uses: Potent and reliable antihypertensive Diluted to a concentration of 100 µg/mL. In patients with renal failure, accumulation of large amounts of thiocyanate may result in thyroid dys- function, muscle weakness, nausea, hypoxia, and acute toxic psychosis. The last of the three cyanide reactions is respon- sible for the development of acute cyanide toxic- ity, which is characterized by metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content (inability to utilize oxygen). Another early sign of cyanide toxicity is the acute resistance to the hypotensive effects of escalating doses of sodium nitroprusside (tachyphylaxis). Cyanide toxicity can usually be avoided if cumulative dose of sodium nitroprusside is less than 0. Pharmacologic treatment of cyanide toxicity: Aim to shunt cyanide away from cytochrome oxidase. Sodium thiosulfate (150 mg/kg over 15 min) 3% sodium nitrate (5 mg/kg over 5 min): Oxidizes hemoglobin to methemoglobin Hydroxocobalamin: Combines with cyanide to form cyanocobalamin (vitamin B ) 12 Methemoglobinemia from excessive doses of sodium nitroprusside or sodium nitrate can be treated with methy- lene blue (1–2 mg/kg of a 1% solution over 5 min); reduces methemoglobin to hemoglobin. Reflex-mediated tachycardia and contractility (offset the favorable changes in myocardial oxygen requirements). Dilation of coronary arterioles by sodium nitroprusside may result in an intracoronary steal of blood away from ischemic areas that are already maximally dilated. Intracranial hypertension may be minimized by slow administration and hyperventilation or hypocapnia. Reductions in pulmonary artery pressure decrease perfusion to normally ventilated alveoli, thereby physiologic dead space = V/Q mismatch and arterial oxygenation. Inhibits hypoxic pulmonary vasoconstriction: V/Q mismatch and arterial oxygenation. Nitroglycerin: Effect on Organ Systems Cardiac: Preload (venous dilation) and afterload (arteriolar dilation); reduces myocardial oxygen demand, increases myocardial supply. Pooling of blood in large-capacitance vessels, venous return, preload, ventricular end-diastolic pres- sure = myocardial oxygen demand and endocardial perfusion. Reminder: A significant decrease in diastolic pressure may lower coronary perfusion and actually decrease myocardial oxygen supply. Nitroglycerin redistributes coronary blood flow to ischemic areas of subendocardium. Profound preload reduction is very useful in relieving cardiogenic pulmonary edema. Heart rate is largely unchanged; rebound hypertension less likely after discontinuation (in contrast with sodium nitroprusside). They are weak bases, usually with a positive charge at the tertiary amine group at physiological pH. Physicochemical properties are determined by linkage, substitutions in the aromatic ring, and alkyl groups attached to the amine nitrogen. Mechanism of Action Neurons have voltage-gated Na channels that can produce and transmit membrane depolarization along the nerve membrane after chemical, mechanical, or electrical stimuli. All local anesthetics bind the α subunit of the transmembrane Na channel on nerve fibers and inhibit the voltage-gated Na channels from activation and Na influx associated with membrane depolarization. At high enough local anesthetic concentrations and with a sufficient fraction of local anesthetic-bound Na channels, an action potential can no longer be generated because Na cannot cross the membrane, and impulse propagation is abolished. Available Preparations Generally prepared commercially as water-soluble hydrochloride salts (pH of 6–7). Because epinephrine is unstable in alkaline environments, epinephrine-containing local anesthetics are more acidic (pH of 4–5) with a lower concentration of free base and a slower onset. Small diameter and myelination increases sensitivity to local anesthetics so that smaller, unmyelinated Aδ fibers are more sensitive than larger unmyelinated Aα fibers.